Autophagy reports最新文献_第6页

Chaperone-mediated autophagy dysfunction in imiquimod-induced psoriasiform dermatitis. 伴蛋白介导的自噬功能障碍在吡喹莫德诱导的银屑病样皮炎。

Autophagy reports Pub Date : 2025-08-25 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2544061

Wei Zhao, Kainan Liao, Wei Song, Jing Wang, Chunlin Cai, Fusheng Zhou, Dandan Zang, Deping Xu, Haisheng Zhou

{"title":"Chaperone-mediated autophagy dysfunction in imiquimod-induced psoriasiform dermatitis.","authors":"Wei Zhao, Kainan Liao, Wei Song, Jing Wang, Chunlin Cai, Fusheng Zhou, Dandan Zang, Deping Xu, Haisheng Zhou","doi":"10.1080/27694127.2025.2544061","DOIUrl":"10.1080/27694127.2025.2544061","url":null,"abstract":"Psoriasis is a chronic inflammatory skin disease characterized by abnormal differentiation and hyperproliferation of epidermal keratinocytes. Autophagy plays a critical role in regulating the functions of immune cells, endothelial cells, and especially keratinocytes, contributing to the pathogenesis of psoriasis. However, the role of chaperone-mediated autophagy (CMA) in psoriatic keratinocytes has not been fully explored. Our study, for the first time, revealed that defective CMA is present in imiquimod (IMQ)-induced psoriasiform lesions. Importantly, activation of CMA significantly attenuated IMQ-induced phenotypes both in vitro and in vivo, including reduced skin lesion severity, decreased keratinocyte proliferation and differentiation, and lower cytokine secretion. Mechanistically, toll-like receptor 7 (TLR7), containing a specific KFERQ-like motif, is a substrate for CMA-mediated degradation. This process modulates IMQ-TLR7 signal activation in keratinocytes. CMA deficiency in psoriasis leads to increased TLR7 levels, which, in turn, enhances TLR7-NF-κB signaling pathway activation, ultimately contributing to dysregulated keratinocyte proliferation, differentiation, and cytokine secretion. This study provides novel evidence that defective CMA is present in IMQ-induced psoriasiform lesions and that CMA activation can attenuate IMQ-induced phenotypes by modulating TLR7 signaling in keratinocytes. These findings highlight the potential of CMA as a therapeutic target for psoriasis.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2544061"},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sequestering sequestosome 1 via S-acylation in autophagy, Huntington disease, and beyond. 在自噬、亨廷顿病及其他疾病中通过s -酰化隔离封存体1。

Autophagy reports Pub Date : 2025-08-25 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2547975

Y Alshehabi, F Abrar, D D O Martin

{"title":"Sequestering sequestosome 1 via S-acylation in autophagy, Huntington disease, and beyond.","authors":"Y Alshehabi, F Abrar, D D O Martin","doi":"10.1080/27694127.2025.2547975","DOIUrl":"10.1080/27694127.2025.2547975","url":null,"abstract":"Protein mislocalization and aggregation are hallmark features in neurodegeneration. As proteins mislocalize, proteostasis deficiency and protein aggregation typically follow. Autophagy is a crucial pathway for the removal of protein aggregates to maintain neuronal health, but is impaired in various neurodegenerative diseases, including Huntington disease (HD). We identified S-acylation, a reversible lipid modification of proteins, as an important regulator in protein trafficking and autophagy. SQSTM1 (sequestosome 1/p62) is an essential selective autophagy receptor for the sequestration of ubiquitinated cargoes within autophagosomes and subsequent delivery into lysosomes for degradation. Recently, we reported that S-acylation of SQSTM1 at the di-cysteine motif C289,290 directs SQSTM1 to lysosomes. We further showed that SQSTM1 S-acylation is significantly reduced in brains from both HD patients and mouse HD model, which may result in the cargo sequestration defect within autophagosomes in HD. Treatment with palmostatin B, a deacylation inhibitor, significantly increases SQSTM1 localization to lysosomes. Our work highlights SQSTM1 S-acylation as a novel potential therapeutic strategy in HD. As a crucial autophagy component, our work suggests S-acylation of SQSTM1 may have a broader role in neurodegeneration.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2547975"},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

During Aspergillus nidulans nitrogen-limited biofilm formation, mitophagy is independent of mitochondrial fission. 在中性曲霉氮限制生物膜形成过程中，线粒体自噬独立于线粒体裂变。

Autophagy reports Pub Date : 2025-08-22 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2547194

Hari Krishnan Balasubramanian, Stephen A Osmani

{"title":"During Aspergillus nidulans nitrogen-limited biofilm formation, mitophagy is independent of mitochondrial fission.","authors":"Hari Krishnan Balasubramanian, Stephen A Osmani","doi":"10.1080/27694127.2025.2547194","DOIUrl":"10.1080/27694127.2025.2547194","url":null,"abstract":"During chronic infections, biofilms are resistant to both antimicrobial agents as well as the host immune system, often giving rise to recalcitrant persister cells with reduced mitochondrial function rendering biofilm infections difficult to cure. How mitochondrial dynamics and fate are regulated during fungal biofilm formation is poorly understood. In this study, we used live cell microscopy to track mitochondrial morphology during Aspergillus nidulans in vitro biofilm formation. We show that mitochondria undergo fragmentation during early biofilm development, and that externally induced oxidative stress similarly induces mitochondrial fragmentation, indicating a role for redox regulation in this process. Deletion of core components of the mitochondrial fission machinery resulted in a swollen mitochondrial phenotype. Mitochondria in the fission-mutant strains are known not to complete fragmentation in response to externally induced oxidative stress, and we show that this results in a \"beads on a string\" phenotype. We further show that mitochondria remain unfragmented during biofilm formation in the fission-mutant strains, although other biofilm cellular modifications, like disassembly of microtubules, are unaffected. We report that mitophagy is triggered during biofilm development in nitrogen-limiting conditions independently of mitochondrial fission. This indicates mitochondrial fission is dispensable for mitophagy during biofilm development with limiting nitrogen. We further note that general autophagy, but notably not mitophagy, is triggered during biofilm development in carbon-limiting conditions, demonstrating differential regulation of mitochondrial fate in response to specific nutritional limitations during fungal biofilm formation.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2547194"},"PeriodicalIF":0.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell type-specific autophagy in human leukocytes: signatures of aging, sex, and nutrient restriction. 人类白细胞中细胞类型特异性自噬：衰老、性别和营养限制的特征。

Autophagy reports Pub Date : 2025-08-17 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2543560

Linh Vp Dang, Timothy J Sargeant

{"title":"Cell type-specific autophagy in human leukocytes: signatures of aging, sex, and nutrient restriction.","authors":"Linh Vp Dang, Timothy J Sargeant","doi":"10.1080/27694127.2025.2543560","DOIUrl":"10.1080/27694127.2025.2543560","url":null,"abstract":"Macroautophagy (referred to here as autophagy) is thought to play a critical role in aging and age-related disease, making it a priority for development of targeted human therapies. We developed a flow cytometry-based method to measure autophagic flux in 19 subpopulations from whole blood, using chloroquine (CQ) to inhibit lysosomal degradation, and the autophagy protein MAP1LC3B (microtubule associated protein 1 light chain 3 beta) isoform II/LC3B-II to measure autophagic flux (the acquisition and degradation of autophagic cargo over time). Autophagic flux varies by cell type and is higher in whole blood compared with RPMI culture media. Basal autophagic flux shows sex- and age-specific variations. Further, monocytes, but not T cells, respond robustly to amino acid starvation by increasing autophagy, with older individuals exhibiting stronger responses, particularly in non-classical monocytes. These findings underscore the importance of cell type-specific autophagy measurements to understand the effects of aging, sex and nutrition, to develop targeted interventions for age-related diseases.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2543560"},"PeriodicalIF":0.0,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biarylacetamides: a novel class of late-stage autophagy inhibitors. 双芳基乙酰酰胺：一类新的晚期自噬抑制剂。

Autophagy reports Pub Date : 2025-08-07 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2541597

Mélissa Lallier, Rani Robeyns, Freke Mertens, Angela Sisto, Guido R Y De Meyer, Koen Augustyns, Maya Berg, Winnok H De Vos, Vincent Timmerman, George M C Janssen, Peter van Veelen, Alexander L N van Nuijs, Nikolai Engedal, Wim Martinet, Pieter Van der Veken

{"title":"Biarylacetamides: a novel class of late-stage autophagy inhibitors.","authors":"Mélissa Lallier, Rani Robeyns, Freke Mertens, Angela Sisto, Guido R Y De Meyer, Koen Augustyns, Maya Berg, Winnok H De Vos, Vincent Timmerman, George M C Janssen, Peter van Veelen, Alexander L N van Nuijs, Nikolai Engedal, Wim Martinet, Pieter Van der Veken","doi":"10.1080/27694127.2025.2541597","DOIUrl":"10.1080/27694127.2025.2541597","url":null,"abstract":"Targeting autophagy is believed to hold great promise for the treatment of various diseases, including cancer. However, since the therapeutic efficacy of currently available autophagy-modulating drugs is limited by off-target effects and the requirement of high dosage, there is an urgent need to develop novel autophagy-targeting compounds. In this study, we report molecules of the biarylacetamide class as novel autophagy inhibitors. These molecules were identified via phenotypic high-throughput screening, and a series of analogues was subsequently synthesized. Among these, 5d and 5j were retained as potent autophagy blockers in HeLa and LNCaP cells. Both compounds inhibited autophagy at a late-stage in the pathway, as evidenced by the strong accumulation of RFP-GFP-LC3 puncta as well as LC3-II, GABARAP-II and SQSTM1 protein levels, resembling the effects obtained with the well-known late-stage autophagy inhibitor Bafilomycin A1. Quantitative proteome profiling combined with metabolomic and lipidomic studies revealed that 5j significantly altered lipid metabolism. These alterations included activation of the cholesterol biosynthesis pathway and changes in the distribution of key lipid classes, such as phospholipids, ceramides and triglycerides. Further mechanistic studies indicated that 5d and 5j triggered an ER stress response and may impair lysosomal function, as suggested by the accumulation of pro-cathepsin D. Collectively, these findings demonstrate that 5j is a novel and potent late-stage autophagy inhibitor with a distinct mechanism of action compared to currently available inhibitors.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2541597"},"PeriodicalIF":0.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of autophagy in the pathogenesis and treatment of multiple sclerosis. 自噬在多发性硬化发病机制和治疗中的作用。

Autophagy reports Pub Date : 2025-07-22 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2529196

Giulio Righes, Luana Semenzato, Konstantinos Koutsikos, Veronica Zanato, Paolo Pinton, Carlotta Giorgi, Simone Patergnani

{"title":"The role of autophagy in the pathogenesis and treatment of multiple sclerosis.","authors":"Giulio Righes, Luana Semenzato, Konstantinos Koutsikos, Veronica Zanato, Paolo Pinton, Carlotta Giorgi, Simone Patergnani","doi":"10.1080/27694127.2025.2529196","DOIUrl":"10.1080/27694127.2025.2529196","url":null,"abstract":"Autophagy is a crucial cellular process responsible for the degradation and recycling of damaged or unnecessary components, maintaining cellular homeostasis and protecting against stress. Dysregulation of autophagy has been implicated in a variety of neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Various types of autophagy exist, each with distinct mechanisms, such as macroautophagy, mitophagy, lipophagy, and chaperone-mediated autophagy. These processes are essential for the removal of toxic substrates like protein aggregates and dysfunctional mitochondria, which are vital for neuronal health. In neurodegenerative diseases, the impairment of these clearance mechanisms leads to the accumulation of harmful substances, which accelerate disease progression. Modulating autophagy has emerged as a promising therapeutic strategy, with ongoing studies investigating molecules that can either stimulate or regulate this process. However, despite its potential, significant challenges remain in translating preclinical findings into clinically effective treatments. In this review, we will explore the different types of autophagy, their roles in neurodegenerative diseases, and the therapeutic potential associated with modulating these processes.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2529196"},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential response of neurons to autophagy modulation in Huntington's disease. 亨廷顿舞蹈病中神经元对自噬调节的差异反应。

Autophagy reports Pub Date : 2025-06-30 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2519102

Ankit Sharma, Sushma Rao, Ravi Manjithaya, Vasu Sheeba

{"title":"Differential response of neurons to autophagy modulation in Huntington's disease.","authors":"Ankit Sharma, Sushma Rao, Ravi Manjithaya, Vasu Sheeba","doi":"10.1080/27694127.2025.2519102","DOIUrl":"10.1080/27694127.2025.2519102","url":null,"abstract":"Huntington's disease (HD) is caused by the expansion of poly-glutamine repeats in the Huntingtin (Htt) gene and is associated with a wide variety of motor and physiological (sleep, metabolism, etc.) perturbations. Studies from diverse model organisms have proposed that modulation of autophagy (a key protein homeostatic pathway) can mitigate the toxic effects of mutant HTT protein. However, consistent changes are not observed across studies, and the improvements in phenotypes can be associated with changes in specific circuits/neurons affected by the mutant HTT protein. They suggest that not all neurons respond effectively to autophagy modulation. Hence, it remains to be understood whether diverse circuits/neurons affected by mutant HTT protein respond effectively to this intervention. Using a genetic approach, we expressed mutant HTT protein independently in diverse sets of neurons in male Drosophila melanogaster and asked whether genetic modulation of autophagy pathway through Atg8a overexpression can mitigate the toxic effect of mutant HTT protein. We found that in male flies, not all neurons/circuits expressing mutant HTT protein respond effectively to ATG8a protein. Circadian neurons and neurons regulating carbohydrate and lipid metabolism (Dilp2 +ve) showed improvement, while motor and neurons responding to temperature changes showed no improvement. Using cellular markers we also showed that these phenotypes can be attributed to specific changes in mutant HTT and Ref(2)P proteins (autophagy marker). Our study suggests that not all circuits respond effectively to autophagy modulation and suggests a potential cause for low success of autophagy modulators in clinical trials..","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2519102"},"PeriodicalIF":0.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ADP ribosylation factor-like GTPase 6-interacting protein 5 (ARL6IP5): a prenylated Rab acceptor protein 1 (PRA1) family protein that shapes the ER membrane and regulates ER-phagy. ADP核糖基化因子样GTPase 6-相互作用蛋白5 (ARL6IP5)：一个戊基化的Rab受体蛋白1 （PRA1）家族蛋白，形成内质网膜并调节内质网吞噬。

Autophagy reports Pub Date : 2025-06-10 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2513466

Yasunori Yamamoto, Toshiaki Sakisaka

{"title":"ADP ribosylation factor-like GTPase 6-interacting protein 5 (ARL6IP5): a prenylated Rab acceptor protein 1 (PRA1) family protein that shapes the ER membrane and regulates ER-phagy.","authors":"Yasunori Yamamoto, Toshiaki Sakisaka","doi":"10.1080/27694127.2025.2513466","DOIUrl":"10.1080/27694127.2025.2513466","url":null,"abstract":"The prenylated Rab acceptor protein 1 (PRA1) domain is a conserved domain encompassing four transmembrane domains (TMDs). ARL6IP5 (ADP ribosylation factor-like GTPase 6-interacting protein 5) is a member of the PRA1 family and interacts with the reticulon-homology domain (RHD)-containing proteins including ARL6IP1 (ADP ribosylation factor-like GTPase 6-interacting protein 1) and FAM134B. The RHD is a conserved domain encompassing two short hairpin TMDs and acts as a membrane-shaping unit for endoplasmic reticulum (ER) morphology and ER-phagy. However, the involvement of ARL6IP5 in ER morphology and ER-phagy remains unclear. We recently characterized ARL6IP5 as an ER membrane-shaping protein and found that ARL6IP5 constricts the ER membrane in a manner similar to ARL6IP1, possibly via short hairpin configuration of the TMDs in the PRA1 domain. ARL6IP5 also plays a redundant role with ARL6IP1 in shaping the ER membrane. Importantly, depletion of ARL6IP5 impaired FAM134B-meadited ER-phagy, which is reminiscent of ARL6IP1 depletion. These results suggested that ARL6IP5 acts as an ER membrane-shaping protein that regulates ER-phagy, underscoring the importance of the PRA1 domain. Although ARL6IP5 and ARL6IP1 are confusable protein names and seem to have similar roles in ER-phagy, we clarify in this punctum that they are distinct classes of ER membrane-shaping proteins.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2513466"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Autophagy-enhancing strategies to promote intestinal viral resistance and mucosal barrier function in SARS-CoV-2 infection. 自噬增强策略在SARS-CoV-2感染中促进肠道病毒耐药性和粘膜屏障功能

Autophagy reports Pub Date : 2025-06-10 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2514232

Anusca G Rader, Alexandra P M Cloherty, Kharishma S Patel, Dima D A Almandawi, Jimena Perez-Vargas, Manon E Wildenberg, Vanesa Muncan, Renée R C E Schreurs, François Jean, Carla M S Ribeiro

{"title":"Autophagy-enhancing strategies to promote intestinal viral resistance and mucosal barrier function in SARS-CoV-2 infection.","authors":"Anusca G Rader, Alexandra P M Cloherty, Kharishma S Patel, Dima D A Almandawi, Jimena Perez-Vargas, Manon E Wildenberg, Vanesa Muncan, Renée R C E Schreurs, François Jean, Carla M S Ribeiro","doi":"10.1080/27694127.2025.2514232","DOIUrl":"10.1080/27694127.2025.2514232","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 19 (COVID-19), continues to circulate globally despite the widespread vaccination and therapeutics like Paxlovid, remdesivir, and molnupiravir. COVID-19 is associated with both respiratory and gastrointestinal manifestations, with persistent intestinal pathology contributing to the post-COVID-19 condition. We have previously demonstrated the antiviral activity of autophagy-blocking drugs, such as Berbamine dihydrochloride, against intestinal SARS-CoV-2 acquisition. In addition, the autophagy blockers restored the barrier function of infected intestinal epithelium. In this addendum, using human intestinal organoids, we present evidence for a protective role of intrinsic higher levels of autophagy flux in limiting intestinal SARS-CoV-2 infection. Pharmacological treatment with Akt inhibitor MK-2206 hydrochloride suppressed viral entry into the intestinal epithelium. This antiviral effect of MK-2206 was shown to be dependent on Synaptosomal-associated protein 29-dependent (SNAP-29)-mediated autophagy flux. Furthermore, extrinsically enhanced autophagy with MK-2206 also prevented SARS-CoV-2-induced intestinal barrier damage. Our findings thus underscore the intricate role of autophagy pathways in the dissemination and pathogenesis of intestinal SARS-CoV-2, highlighting the therapeutic potential of host-directed therapies targeting autophagy to intervene in COVID-19-associated sequelae and improve intestinal health.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2514232"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Small but mighty: ATG9A-positive vesicles are a branch of the intracellular nanovesicle superfamily. 小而强大：atg9a阳性囊泡是细胞内纳米囊泡超家族的一个分支。

Autophagy reports Pub Date : 2025-06-04 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2513467

Mary Fesenko, Stephen J Royle

{"title":"Small but mighty: ATG9A-positive vesicles are a branch of the intracellular nanovesicle superfamily.","authors":"Mary Fesenko, Stephen J Royle","doi":"10.1080/27694127.2025.2513467","DOIUrl":"10.1080/27694127.2025.2513467","url":null,"abstract":"The molecular and functional characterization of the thousands of uncoated intracellular transport vesicles inside cells is a major challenge. Intracellular nanovesicles (INVs) are a large and molecularly heterogenous family of uncoated transport vesicles, which are comprised of multiple subtypes. As a step to characterizing these subtypes, we recently published the first INV proteome and were intrigued by the enrichment of ATG9A in it. ATG9A is the only conserved transmembrane protein with a core function in macroautophagy/autophagy, and it is found on small, uncoated vesicles, termed \"ATG9A-positive vesicles\". We therefore, set out to disambiguate the relationship between these two types of vesicular carriers in cells. We showed that ATG9A-containing vesicles, rather than being a distinct vesicle class, represent one subset of the INV family. We also demonstrated that this relationship is functionally important and that perturbing INV-mediated trafficking impeded starvation-induced autophagy. Here, we briefly introduce INVs, summarize the evidence supporting our definition of ATG9A-flavor INVs and present our outlook on why we hope that this classification will help to consolidate efforts to understand the functions of these vesicles in autophagy and beyond.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2513467"},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0